The present invention is related to a ferulate compound and compositions thereof derived from Commiphora wightii or Commiphora mukul, Commiphora sp., and more particularly to methods of using the composition to prevent and/or treat abnormal cell growth and/or proliferation in inflammation, neoplasia and/or cardiovascular disease.
Commiphora mukul, Commiphora wightii, Commiphora sp. (N.O. Burseraceae) is a branched shrub or a small tree (2-3 m high) found in some states of India and Pakistan and known to produce a resinous exudate more commonly referred to as gum guggal. The Commiphora tree is mentioned in the Classic Ayurvedic literature for use in the treatment of bone fractures, arthritis, inflammation, obesity, cardiovascular diseases and lipid disorders. The Ayurvedic medical treatises of Caraka Samhita (1000 BC), Sushruta Samhita (600 BC), Vagbhata (7th century AD) and Nighantusa (12th-14th century AD)) disclose the effects of poor nutrition and a sedentary life style with diminished health. These two factors were reported to contribute to xe2x80x9ccoating and obstruction of channelsxe2x80x9d, or to atheromatous changes including deposition of fatty streaks in the blood vessels. To counteract this pathological process, Ayurveda practitioners prescribed gum guggal obtained from the bark of the Commiphora wightii tree.
In the 1960""s the oleogum resin (gum guggul) was studied for its potential in the treatment of elevated blood cholesterol or hyperlipidemia. This research originated from the College of Medical Sciences of Banaras Hindu Univeristy at Varanasi, India, and was continued into the 1980""s at the Central Drug Research Institute (CDRI) at Lucknow, India. Based on the structure function analysis of gum guggul, it was determined that the soluble portion of the gum is ethyl acetate, and specifically its neutral portion, contained most of the hypolipidemic properties. The neutral fraction was found to be a source of sterol compounds known as guggulsterone Z and E (pregnane derivatives) and responsible for lowering of blood cholesterol. Subsequently, the preparation of gum guggul used by the CDRI in clinical studies consisted of a solid extract, standardized to contain a minimum of 2.5% guggulsterones E and Z (Indian Pharmacopea, 1988; Satyavati, 1991).
With the discovery of the hypolipidemic activity for the gum resin, several chemical investigations were undertaken. It was found that guggul resin is a complex mixture of various classes of chemical compounds such as lignans, lipids, diterpenoids and plant steroids. A waxy solid comprising a mixture of esters (FIG. 1) based on homologous long chain tetraols and ferulic acid with a unique structure, was identified in the benzene phase (Satyavati, 1991). In a more detailed study by Kumar et al. (1987), the stereochemistry of these tetraols was been determined.
The present invention relates to the purification and identification of novel ferulate compounds obtainable from gum guggul, compositions thereof, and a therapeutic use of the compositions alone or formulated to contain an ethyl acetate fraction from gum guggul comprising gugulsterones Z and E.
Based on systematic study of gum guggul, it has been found that the ethyl acetate fraction of gum guggul shows significant anti-proliferative and antioxidant effects in vitro. In embodiments of the present invention, isolation and identification of the active constituents of this plant and elucidation of their chemical structures and bioactivities is described hereunder.
An object of the present invention is the purification of a ferulate compound from an extract of gum guggul and its formulation into a composition.
Another object of the invention is a process for purifying the ferulate compound.
Another object of the invention is a method for prevention and/or treatment of abnormal cell growth and proliferation in inflammation, neoplasia and cardiovascular disease using the ferulate in a composition with or without a gum guggul extract containing gugulsterones Z and E.